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. 2022 Mar 17;13:1407. doi: 10.1038/s41467-022-28237-4

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — a Gene set enrichment analysis revealed the differential enrichment of genes involved in two main pathways, along the continuum: metabolism and cell cycle/DNA repair. Samples are ordered based on the SV continuum in Fig. 2, with highest patient grade and cohort group denoted at the top. b Median methylation levels for the cohort groups within different regions of the genome in relation to the CpG islands: island, shore (up to 2 kb from CpG island), shelf (2–4 kb from CpG island) and sea (>4 kb from CpG island). N = 100. Boxplot centre line denotes median, box limits are upper and lower quartiles, whiskers denote 1.5* the interquartile range. Statistical significance was calculated using Wilcoxon signed-ranked test. ns non-significant, *p-value < 0.05, **p-value < 0.5, ***p-value < 0.001. c Integrated gene expression and methylation data. Patients are aligned along the same SV continuum order. Thirty-seven genes related to the Wnt signalling and cell cycle pathways for which altered expression followed a gain in promoter methylation and for which there was a significant change in expression with progression.